T-cell lymphopenia is associated with an increased infecting risk in children after cardiopulmonary bypass.

BACKGROUND: children who undergo CPB operations are at an elevated risk of infection due to immunosuppression. This study aims to investigate the association between lymphopenia following CPB and early postoperative infection in children. METHODS: A retrospective analysis including 41 children under 2 years old underwent CPB. Among them, 9 subjects had an early postoperative infection, and 32 subjects were period-matched without infection. Inflammatory cytokines, serum CRP and PCT values were measured in plasma, additionally, circulating total leucocyte and lymphocyte subpopulations were counted. RESULTS: Infected subjects exhibited significantly higher levels of inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1ß and TNF-α, than non-infected subjects after CPB. Additionally, lower absolute number of lymphocyte and their subpopulations CD3+ T cells, CD4+ T-helper cells and CD8+cytotoxic T-cells, were observed in infected subjects. The impairment of T-cells Immune was found to be associated with higher levels of inflammatory cytokines IL-10. The ROC demonstrated that the absolute number of CD3+ T-cells <1934/ul, CD4+ T helper cells <1203/ul and CD8+cytotoxic T-cells <327/ul were associated with early postoperative infection. CONCLUSION: Higher levels of inflammatory cytokines resulted in T-cells lymphopenia after CPB, which significantly increasing the risk of postoperative infection in infants and young children. IMPACT: Infection complications after cardiopulmonary bypass (CPB) in pediatric CHD patients are serious issues, identifing the infection from after CPB remains a challenging. CPB can release numerous inflammatory cytokines associated with T cells lymphopenia, which increases the risk of postoperative infection after surgery. Monitoring T cells lymphopenia maybe more beneficial to predict early postoperative infection than C-reactive protein and procalcitonin.

Analysis of pathogenic variants in 605 Chinese children with non-syndromic cardiac conotruncal defects based on targeted sequencing.

OBJECTIVE: Deleterious genetic variants comprise one cause of cardiac conotruncal defects (CTDs). Genes associated with CTDs are gradually being identified. In the present study, we aimed to explore the profile of genetic variants of CTD-associated genes in Chinese patients with non-syndromic CTDs. METHODS: Thirty-nine CTD-related genes were selected after reviewing published articles in NCBI, HGMD, OMIM, and HPO. In total, 605 patients with non-syndromic CTDs and 300 healthy controls, all of Han ethnicity, were recruited. High-throughput targeted sequencing was used to detect genetic variants in the protein-coding regions of genes. We performed rigorous variant-level filtrations to identify potentially damaging variants (Dvars) using prediction programs including CADD, SIFT, PolyPhen-2, and MutationTaster. RESULT: Dvars were detected in 66.7% (26/39) of the targeted CTD-associated genes. In total, 11.07% (67/605) of patients with non-syndromic CTDs were found to carry one or more Dvars in targeted CTD-associated genes. Dvars in FOXH1, TBX2, NFATC1, FOXC2, and FOXC1 were common in the CTD cohort (1.5% [9/605], 1.2% [7/605], 1.2% [7/605], 1% [6/605], and 0.5% [3/605], respectively). CONCLUSION: Targeted exon sequencing is a cost-effective approach for the genetic diagnosis of CTDs. Our findings contribute to an understanding of the genetic architecture of non-syndromic CTDs.

Positional Relationship Between the Pulmonary Venous Confluence-Vertical Vein and Atria in Infracardiac Total Anomalous Pulmonary Venous Connection.

To explore the positional relationship between the pulmonary venous confluence-venous vein (PVC-VV) and both the atria in infracardiac total anomalous pulmonary venous connection (iTAPVC), using two-dimensional (2D) computerized tomography (CT) reconstruction. Through the 2D reconstruction of enhanced cardiac CT images of patients with iTAPVC, the projection of PVC-VV on coronal axial images was acquired and its location on the bilateral atrial splice was analyzed. Sagittal axial reconstruction was used to identify which atrium had a precise anterior-posterior positional relationship with PVC-VV. The type of iTAPVC, where the projection of PVC-VV was lying on the left atrium, and the left atrium had a precise anterior-posterior positional relationship with PVC-VV, was classified as the left atrial type. If the projection of PVC-VV was lying on the right atrium and the right atrium had a precise anterior-posterior positional relationship with PVC-VV, it was classified as the right atrial type. Finally, if the projection of PVC-VV was lying in the middle of the bilateral atria, and both the atria had precise anterior-posterior positional relationship with PVC-VV, it was referred to as the bilateral atrial type. Upon analysis of the 22 enhanced cardiac CT images, 6 were the left atrial type (27.27 %), 9 were right atrial type (40.91 %), while 7 were of the bilateral atrial type (31.82 %). The positional relationship between PVC-VV and the bilateral atria are variable, and iTAPVC classification using 2D CT reconstruction is an invaluable tool in designing the surgical approaches in iTAPVC.

Ventriculo-arterial coupling for predicting cardiac index increase in infants after heart surgery.

OBJECTIVES: The aim of this study was to test the ability of ventriculo-arterial coupling (VAC) to predict cardiac index (CI) response after milrinone infusion. METHODS: This was a retrospective, observational study. We measured arterial blood pressure and echocardiography-derived variables, including CI, systemic vascular resistance index, arterial elastance (Ea) and end-systolic ventricular elastance before and after 18-24 h of milrinone infusion. VAC was calculated as the ratio of Ea to end-systolic elastance. Infants with over 15% increase in the CI were defined as CI responders. Logistical regression was used to evaluate predictors of CI responders. RESULTS: We enrolled 92 infants who underwent cardiac surgery and received milrinone infusion, of whom 45 infants were CI responders. High VAC (odds ratio = 5.534, 95% confidence interval 2.339-13.090) and high Ea (odds ratio = 3.035, 95% confidence interval 1.459-6.310) were independently associated with cardiac index responders. Pre-milrinone VAC predicted CI responsiveness with a cut-off value of 1.12 (area under the curve = 0.900, 95% confidence interval 0.819-0.953, P < 0.0001). Furthermore, we observed a decrease in the infant's VAC, Ea and systemic vascular resistance index after milrinone infusion. CONCLUSIONS: In infants with congenital heart disease after surgery, a pre-milrinone VAC >1.12 can predict the increase in the CI following milrinone infusion.

Two genetic variants in NEXN and ABCC6 genes found in a patient with right coronary artery to right ventricle fistula combined with giant coronary aneurysm and patent ductus arteriosus.

Objective: Coronary artery fistula, defined as communication between a coronary artery and a great vessel or a cardiac chamber, is a relatively rare anomaly with an estimated incidence of 0.002% in the general population. It could be combined with a giant coronary artery aneurysm, with an incidence of 5.9% of the total incidence rate of CAF in the general population. The pathogenesis of these two combined anomalies is not clear, and we aimed to detect whether genetic abnormalities underlie the pathogenesis of these rarely combined anomalies. Materials and methods: A 6-year-old patient with a diagnosis of the right coronary artery to right ventricle fistula combined with a giant right coronary artery aneurysm and patent ductus arteriosus underwent a surgical repair at our center. The diagnosis was confirmed by echocardiography, CT, and surgery. DNA was extracted from the peripheral venous blood samples of the patient and his mother after informed consent was obtained. Hematoxylin and Eosin (HE) and Alizarin red staining were performed on the excised coronary artery aneurysm. Exome sequencing and in silico analyses were performed to detect detrimental genetic variants. Results: No obvious abnormalities were found in the excised coronary artery aneurysm. A heterozygous truncated variant (NM_144573: c.G298T; p.G100X) in the NEXN gene and a missense variant (NM_001171: c.G1312A; p.V438M) in the ABCC6 gene were carried by the patient but not by his mother. Conclusion: The NEXN-truncated variant, NEXN-G100X, is associated with the development of coronary arteries and congenital coronary artery anomalies.

Gelatin/Polycaprolactone Electrospun Nanofibrous Membranes: The Effect of Composition and Physicochemical Properties on Postoperative Cardiac Adhesion.

Cardiovascular diseases have become a major threat to human health. The adhesion formation is an inevitable pathophysiological event after cardiac surgery. We have previously shown that gelatin/polycaprolactone (GT/PCL, mass ratio 50:50) electrospun nanofibrous membranes have high potential in preventing postoperative cardiac adhesion, but the effect of GT:PCL composition on anti-adhesion efficacy was not investigated. Herein, nanofibrous membranes with different GT:PCL mass ratios of 0:100, 30:70, 50:50, and 70:30 were prepared via electrospinning. The 70:30 membrane failed to prevent postoperative cardiac adhesion, overly high GT contents significantly deteriorated the mechanical properties, which complicated the suturing during surgery and hardly maintained the structural integrity after implantation. Unexpectedly, the 0:100 membrane (no gelatin contained) could not effectively prevent either, since its large pore size allowed the penetration of numerous inflammatory cells to elicit a severe inflammatory response. Only the GT:PCL 50:50 membrane exhibited excellent mechanical properties, good biocompatibility and effective anti-cell penetration ability, which could serve as a physical barrier to prevent postoperative cardiac adhesion and might be suitable for other biomedical applications such as wound healing, guided tissue or bone regeneration.

Orthogonally Functionalizable Polyurethane with Subsequent Modification with Heparin and Endothelium-Inducing Peptide Aiming for Vascular Reconstruction.

Surface coimmobilization modifications of blood-contacting devices with both antithrombogenic moieties and endothelium-inducing biomolecules may create a synergistic effect to improve their performance. However, it is difficult to perform covalent dual-functionalization with both biomolecules on the surface of normally used synthetic polymeric substrates. Herein, we developed and characterized an orthogonally functionalizable polymer, biodegradable elastic poly(ester urethane)urea with disulfide and amino groups (PUSN), which was further fabricated into electropun fibrous scaffolds and surface modified with heparin and endothelial progenitor cells (EPC) recruiting peptide (TPS). The modification effects were assessed through platelet adhesion, EPC, and HUVEC proliferation. Results showed the dual modified PUSN scaffolds demonstrated a synergistic effect of reduced platelet deposition and improved EPC proliferation in vitro study, and demonstrated their potential application in small diameter vascular regeneration.